Inclusion complex formation of anthracycline antibiotics with cyclodextrins; a proton nuclear magnetic resonance and molecular modelling study

The inclusion complexation of the anthracyline antibiotics doxorubicin and daunorubicin with cyclodextrins has been studied by proton NMR and molecular modelling. The anthracyclines were found to complex with -cyclodextriny-cyclodextrin, whereby the aglyconic part of the molecule is included in the cyclodextrin cavity. Job ratio plots based on NMR data indicate that the complex has a stoichiometry of 1 : 1. Complex constant values of 345 M^–1 and 323 M^–1 (at pH 3) were found for doxorubicin and daunorubicin, respectively.     

Reaktionen von fulvenen mit 1,3-dipolaren verbindungen. IV . Umsetzung des 6,6-diphenylfulvens mit 2,4,6-triphenylpyrylium-3-olat

6,6-Diphenylfulvene (6) reacts with 2,4,6-triphenylpyrylium-3-olate (7) to give three [π2 + π-4] cyclo-adducts 8, 9, 10. Reduction of 8 with sodium borohydride yields a cage-like compound 12 whereas the action of the same reagent on 9 results in the formation of three carbinols 13, 14, 15 . Treatment of 9 with acetic acid/hydrogen chloride yields an isomer 18 . The structures of both 12 and 18 have been established by X-ray crystallography.     

Enhanced method performance due to a shorter chromatographic run-time in a liquid chromatography-tandem mass spectrometry assay for paclitaxel

Liquid chromatography-tandem mass spectrometry (LC-MS-MS) is often performed in a high-throughput environment. Unfortunately, with atmospheric pressure ionization (API) techniques, shorter run-times or reduced sample clean-up often result in ion or matrix suppression, which can lead to erroneous results. The present work on the analysis of paclitaxel compares ion suppression, sensitivity and linearity of a high-throughput LC-MS-MS method (0.8 min run-time, method B) to a method with increased separation (2.0 min run-time, method A). An atmospheric pressure chemical ionization (APCI) interface was used for both methods. The high-sample-throughput method uses an increased amount of organic solvent in the mobile phase (isocratic, 85% versus 70% of methanol) and a higher flow-rate (600 microl/min versus 400 micro/min). As a result, internal standard (docetaxel) and target analyte (paclitaxel) co-elute, close to, although separated from the solvent front. Ion suppression of both methods was evaluated by comparing pure standard to plasma and plasma containing a vehicle. Sensitivity and linearity were compared by injecting matrix matched calibration samples with both methods. Ion suppression by the vehicle Cremophor EL led to poor data quality for the standard method (A), while for the short method (B), ion suppression was compensated for by the co-eluting internal standard. The short method showed similar linearity but increased sensitivity by at least a factor five. This work provides a strategy to compensate for ion suppression without the use of labeled internal standards. In addition, a better sensitivity and a shorter run-time are noted.     

Fluorénacènes et fluorénaphènes synthèses dans la série des indéno-fluorènes,XVII. Dérivés méthylés du cis-fluorénacène,du trans-fluorénacène et du trans-fluorénaphène

By condensation of the chlorides of the three 9-oxo-fluorene-2-, -3-, and -4-carboxylic acids with 4-bromo-1,2-xylene on one side, and of the chlorides of o-bromobenzoic acid, 2-bromo-4-methyl-benzoic acid and 2-bromo-4,5-dimethyl-benzoic acid with fluorene, 2-methylfluorene and 3-methylfluorene on the other side, followed by direct or indirect cyclisation and by final reduction, several new methyl derivatives of the indenofluorenes I, II and IV are synthesized.     

Characterization of oxygenated derivatives of isoprene related to 2-methyltetrols in Amazonian aerosols using trimethylsilylation and gas chromatography/ion trap mass spectrometry

In the present study, we have tentatively identified the structures of three oxygenated derivatives of isoprene in Amazonian rain forest aerosols as the C(5) alkene triols, 2-methyl-1,3,4-trihydroxy-1-butene (cis and trans) and 3-methyl-2,3,4-trihydroxy-1-butene. The formation of these oxygenated derivatives of isoprene can be explained by acid-catalyzed ring opening of epoxydiol derivatives of isoprene, namely, 1,2-epoxy-2-methyl-3,4-dihydroxybutane and 1,2-dihydroxy-2-methyl-3,4-epoxybutane. The structural proposals of the C(5) alkene triols were based on chemical derivatization reactions and detailed interpretation of electron and chemical ionization mass spectral data, including data obtained from first-order mass spectra, deuterium labeling of the trimethylsilyl methyl groups, and MS(2) ion trap experiments. The characterization of 2-methyl-1,3,4-trihydroxy-1-butene (cis and trans) and 3-methyl-2,3,4-trihydroxy-1-butene in forest aerosols is important from an atmospheric chemistry viewpoint in that these compounds hint at the formation of intermediate isomeric epoxydiol derivatives of isoprene and as such provide mechanistic insights into the formation of the previously reported 2-methyltetrols through photooxidation of isoprene.     

Optimization and validation of an enantioselective method for a chiral drug with eight stereo-isomers in capillary electrophoresis

Highly selective capillary electrophoresis (CE) screening methods were applied to find a satisfactory separation of a chiral drug with eight stereoisomeric compounds. The initial separation conditions were further optimized using response surface modelling by applying a Box-Behnken experimental design. This approach resulted in a rapid and efficient optimization of the buffer concentration, the concentration of two cyclodextrins, and the run voltage, in order to obtain final separation conditions of the method. Further optimization and validation of the system in terms of sensitivity and robustness resulted in a method that is suitable for quality control release purposes.     

Determination of fluoxetine and norfluoxetine in rat brain microdialysis samples following intraperitoneal fluoxetine administration

Fluoxetine (FLX) and the N-desmethyl metabolite, norfluoxetine (NFLX) in rat brain microdialysis samples were determined by high-performance liquid chromatography (HPLC) with fluorescence detection using pre-column derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F). In vitro experiment showed that the relative recovery of FLX across microdialysis membrane was enhanced by adding β-cyclodextrin (β-CD) or β-CD polymer to microdialysis perfusion fluid. The perfusion fluid containing β-CD polymer, which has polymeric glyceryl linkers attached to the hydroxyl group, gave the better recovery with satisfactory precisions. Using 1% β-CD polymer in Ringer’s solution as the perfusate, in vivo rat brain microdialysis experiment on intraperitoneal administration of FLX (10 mg/kg) to rats was carried out. The fluorescence peaks of FLX and NFLX appeared later than 30 min after the administration of FLX, and then, gradually increased with time. Two hours later, FLX reached a plateau level, but NFLX slowly increased, and at 24-48 h, NFLX levels were higher than FLX levels. These data suggest that long distributions of FLX and the potent metabolite, NFLX, in brain contributed to the long-term drug actions in vivo.     

Reduced rings whose finitely generated modules decompose

This paper proves Hua's Theorem and, from this, the Fundamental Theorem of Projective Geometry for the projective line over a commutative ring with “many units”.     

Synthesis of a 6H-Benzofuro[3,2-c][1]benzopyran-6-one. A New Application of the Hurtley Reaction

A copper(I)bromide promoted substitution of 2-bromobenzofuran-3- carboxylic acid (2b) with dimedone and subsequent lactonization offers a new route to a modified coumestane ring system.     

Thin-Layer Chromatographic Determination of Alpha-Amyrin in the Bark of Mallotus philippensis Lamk

JPC – Journal of Planar Chromatography – Modern TLC - A simple, precise, and accurate high-performance thin-layer chro-matographic method has been established for determination of...